AP3D1

Chr 19AR

adaptor related protein complex 3 subunit delta 1

NCBI Gene: 8943ENSG00000065000UniProt: O14617

Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. Involved in process of CD8+ T-cell and NK cell degranulation (PubMed:26744459). In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals (By similarity)

Primary Disease Associations & Inheritance

?Hermansky-Pudlak syndrome 10MIM #617050
AR
568
ClinVar variants
4
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— AP3D1
🧬
Gene-Disease Validity (ClinGen)
Hermansky-Pudlak syndrome 10 · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 250 VUS of 568 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.30LOEUF
pLI 0.986
Z-score 5.97
OE 0.18 (0.11–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.94Z-score
OE missense 0.80 (0.75–0.86)
603 obs / 753.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.11–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.75–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 11 / 61.5Missense obs/exp: 603 / 753.2Syn Z: -2.24

ClinVar Variant Classifications

568 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic1
VUS250
Likely Benign209
Benign98
Conflicting7
3
Pathogenic
1
Likely Pathogenic
250
VUS
209
Likely Benign
98
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
1
0
1
VUS
7
213
27
3
250
Likely Benign
0
2
98
109
209
Benign
0
2
90
6
98
Conflicting
—7
Total7217219118568

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AP3D1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Hermansky-Pudlak syndrome 10

MIM #617050

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — AP3D1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.
Aykut A et al.·Immunol Res
2024
A homozygous AP3D1 missense variant in patients with sensorineural hearing loss as the leading manifestation.
Frohne A et al.·Hum Genet
2023Cohort
Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome.
Ammann S et al.·Blood
2016Case report
Biallelic mutations in AP3D1 cause Hermansky-Pudlak syndrome type 10 associated with immunodeficiency and seizure disorder.
Mohammed M et al.·Eur J Med Genet
2019
Diagnosing Czech Patients with Inherited Platelet Disorders.
Louzil J et al.·Int J Mol Sci
2022Cohort
Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.
Assoum M et al.·Am J Hum Genet
2016
Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing.
Concepcion D et al.·PLoS Genet
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools